Fibrinolytic agents in the management of posthemorrhagic hydrocephalus in preterm infants: the evidence

The objective of this study was to review current literature on the managem ent of posthemorrhagic hydrocephalus in preterm infants with intraventricul ar administration of fibrinolytic agents; to this end a literature search w as carried out electronically. The keywords used were "intraventricular hem orrhage" or "posthemorrhagic hydrocephalus" in combination with "fibrinolyt ic agent," "urokinase," "streptokinase," or "recombinant tissue plasminogen activator" and "intraventricular administration"; the search covered the y ears 1966-1998 and was restricted to English language papers and human subj ects. It was supplemented by a search through the reference lists of the ar ticles identified. Articles dealing with intracerebral hemorrhage or hemato ma, intraventricular hemorrhage in adults, nontherapeutic issues and labora tory research were excluded. The articles included are summarized in eviden ce and evaluation tables. Five scientific publications evaluating the use o f a fibrinolytic agent to manage posthemorrhagic hydrocephalus were retriev ed. In the studies described in these reports, a total of 62 neonates recei ved streptokinase, urokinase or r-tPA intraventricularly. No two of the reg imens were identical in the drug used, method of administration and duratio n of therapy. The time before therapy was started ranged from 2 to 35 days after the ictus. Among the case series reported, three were small series wi th a total of 38 neonates. One other case series of 18 neonates compared th e treatment group with an historical control group. All case series showed that endoventricular fibrinolytic therapy was practical. The proportion of cases in which shunt placement was performed ranged from 11% to 100%. Only one small prospective, randomized, controlled study was identified. That st udy was too small to allow useful conclusions. Overall, 3 cases of secondar y intraventricular hemorrhage were reported. However, it was not possible t o determine with certainty whether these episodes were related to the drug therapy itself. The reports suffer from inadequate study design, lack of de scriptive information and short follow-up period. There is insufficient evi dence to justify the claim that fibrinolytic agents administered intraventr icularly in post-hemorrhagic hydrocephalus are safe and effective. More evi dence is needed to prove or disprove the effectiveness and safety of this f orm of therapy.